Packaging with active protection layer

ABSTRACT

An implantable medical device including a plurality of components on a substrate, and a biocompatible multi-layer coating applied at least in part by vapor deposition to conform to and sealingly cover at least a portion of the components and/or the substrate. The coating is applied in at least two sets of layers, wherein each set has at least one layer formed by dissociation of a polymeric precursor and then deposition of that precursor, and another layer is a biocompatible liquid.

CROSS-REFERENCE TO RELATED APPLICATION

This application claims priority to U.S. Provisional Application No.61/233,395 by Burger et al. filed Aug. 12, 2009 entitled “UltrathinMultilayers for a Hermetic Packaging”. The following applications, filedconcurrently herewith, are incorporated herein by reference: U.S. patentapplication Ser. No. 12/854,298 entitled “Ultra-Thin Multi-LayerPackaging” by Hogg et al.; and U.S. patent application Ser. No.12/854,304 entitled “Plasma Enhanced Polymer Ultra-Thin Multi-LayerPackaging” by Hogg et al.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The invention relates to hermetic biocompatible packaging and moreparticularly to packaging that is deposited in successive layers,including at least one biocompatible liquid layer, overthree-dimensional structures.

2. Description of the Related Art

Packaging which is cost-effective and compatible with miniaturization isan important factor in the production of an implantable medical device.There is a need for a reliable, cost-effective batch-manufacturingpackaging process such as a wafer level packaging, to protect componentssuch as electronic- and mechanical components, micro-electronic- andmechanical systems, micro-electro-mechanical systems and substratescarrying such components. The mentioned packaging must be mechanicallyand chemically stable to protect the body tissue from potentially toxicdissolvents, and also to protect the components of the implanted devicefrom corrosion or degradation created by bodily fluids.

Encapsulation of organic light emitting diodes by at least one barrierstack is disclosed in U.S. Pat. No. 6,570,325 by Graff et al. Thebarrier stack includes at least one barrier layer and at least onedecoupling layer. Other protective barriers which include parylene foropto-electronic devices are disclosed by Lee et al. in U.S. PatentApplication Publication Nos. 2005/0146267, now U.S. Pat. No. 7,364,925,and 2007/0216300, now abandoned.

Techniques for protecting integrated circuits using copolymers formed ofparylene N and co-monomers with various double bonds is disclosed byLang et al. in U.S. Pat. No. 6,709,715. Other, more recent coatingtechniques utilizing parylene are disclosed by Bedinger et al. in U.S.Patent Application Publication No. 2009/0291200 and by Martin, III etal. in U.S. Patent Application Publication Nos. 2009/0263581 and2009/0263641.

A plastic membrane device having micro-structures such as micro-lenses,micro-channels and waveguides utilizing a liquid are disclosed in U.S.Patent Application Publication No. 2009/0246546 by Keppner et al.

It is therefore desirable to provide improved hermetic biocompatiblepackaging, especially for implantable medical devices for whichreduction in size is preferred.

SUMMARY OF THE INVENTION

An object of the present invention is to provide improved, lower-costmulti-layer packaging having low permeability to bodily fluids toprotect both the patient and components beneath the packaging.

Another object of the present invention is enable the implementation ofat least one active agent set in the biocompatible hermetic coating.

A still further object of the present invention is to provide suchpackaging which can be applied to medical devices substantially at roomtemperature to protect the medical devices against temperature defectswhich may otherwise occur at higher application temperatures.

This invention features an implantable medical device including aplurality of components on a substrate, and a biocompatible multi-layercoating applied at least in part by vapour deposition to conform to andsealingly cover at least a portion of the components. The coating isapplied in at least two sets of layers, wherein each set has at leastone layer formed by dissociation of a polymeric precursor and thendeposition of that dissociated precursor, and another layer is abiocompatible liquid.

In a number of embodiments, each layer differs in at least one diffusionbarrier property from the other layer in the set. In some embodiments,diffusion through each layer differs from that of the other layer in theset and adds to the overall barrier effect of the coating. In oneembodiment, the polymeric layer itself is activated for enhancedwetability. In certain embodiments, the precursor for at least one layeris selected from di-p-xylylene and halogenated derivatives thereof toform a type of parylene for that layer. In one embodiment, at least oneof the layers in each set is a plasma-enhanced parylene polymer.

In some embodiments, each of the sets has at least three layers, anddiffusion through each layer differs from that of the other layers inthe set. In one embodiment, at least one of the layers enhanceswetability of the layer beneath it, and the wetability-enhancing layerincludes at least one of chemical and plasma activation of the layerbeneath it.

In another embodiment, the liquid is applied by condensation. In yetanother embodiment, the liquid is applied as a fog or a mist. In a stillfurther embodiment, the liquid is applied by dipping or casting. Theliquid itself acts as an active protection layer by providing a physicaland/or chemical barrier to oxygen, water and/or types of ions, atoms ormolecules in a bi-directional manner; in some embodiments, at least oneliquid layer also includes an active agent such as a pharmaceutical,antimicrobial or other material having a physiological property oractivity. In one embodiment, the multi-layer coating conforms to andsealingly covers at least substantially all of the components, some orall of which may be three-dimensional, and may cover some or all of thesubstrate as well.

BRIEF DESCRIPTION OF THE DRAWINGS

In what follows, preferred embodiments of the invention are explained inmore detail with reference to the drawings, in which:

FIG. 1 is a schematic cross-sectional view of complex, three-dimensionalcomponents and a substrate coated with multiple layers according to thepresent invention;

FIG. 2 is an enlarged cross-sectional view of multiple layers accordingto the present invention protecting a component on a substrate; and

FIG. 3 is a schematic diagram of a reactor system for producingmulti-layer packaging according to the present invention.

DETAILED DESCRIPTION OF THE PRESENTLY PREFERRED EMBODIMENTS

FIG. 1 illustrates an example of components and a substrate of animplantable medical device 20 with three-dimensional conformal packagingaccording to the present invention. Device 20 includes a plurality ofthree-dimensional components, such as transistor 8,micro-electro-mechanical system 9 and conductive bonding 10, on asubstrate 23 which can be flexible or rigid as desired. A biocompatiblemulti-layer coating 22 applied at least in part by vapour depositionconforms to and sealingly covers at least a portion of the components8,9,10 and the substrate 23.

The coating 22 is applied in at least two sets of layers, wherein eachset has at least one layer formed by dissociation of a precursor andthen deposition of that dissociated precursor, also referred to asdeposition of dissociated species of the precursor, and the other layeris a biocompatible liquid. In some constructions, at least one of thelayers is formed by at least one of plasma dissociation and excitationof the precursor to form a plasma-enhanced precursor, and thendeposition of the plasma-enhanced precursor. As illustratedschematically in FIG. 2, coating 22 a is formed in a series of layers 3,4, 5, and 6 over component 2 of device 20 a with substrate 23 a.Additional layers 7 et cetera can be added as desired. At least two setsof layers, such as layers 3 plus 4 and 5 plus 6, have one layer each,such as layers 4 and 6, that are formed of a liquid as described below.In other constructions, each set has at least three layers, such aslayers 3, 4 and 5 in a first set and layers 6, 7 and 7′ (not shown) in asecond set, with one of layers 4 and 5 being a liquid and one of layers7 and 7′ being a liquid. Typically, the outermost layer is a solid layerto retain liquids beneath it or to allow a well-defined diffusion of theliquid beneath it. In some constructions, an additional treatment, suchas a gas plasma, or an additional layer is added to improve theinterface between non-liquid layers, especially with respect to impuritydiffusion.

It is a realization of the inventors that increasing the number and typeof thinner layers, rather than having fewer, thicker layers, enhancesoverall barrier properties of packaging according to the presentinvention due to the increased number of layer interfaces. In otherwords, the sum of the interfaces dominates diffusion behaviour, andtherefore the overall barrier effect of the coating, more than the sumof the thicknesses of the layers. This may also be expressed as thediffusion barrier being composed by the layer interface and each layeritself. As for the physical properties of each layer, polymers such asparylene are especially desirable for being pin-hole-free, homogenous,and stress-free, which is especially advantageous to overlie a liquidlayer. The use of one or more liquid layers according to the presentinvention, and the additional solid/liquid interfaces provided thereby,further adds unique liquid properties to the overall barrier effect ofthe coating.

One system 100 for achieving such conformal packaging with multi-layercoatings is shown in FIG. 3. Deposition reactor chamber 105 can beutilized for a thermal process, such as a conventional or modifiedGorham process, or a plasma enhanced process. For the deposition of aparylene on a liquid layer with a vapour pressure lower than 7 Pa, theconventional Gorham process is used. Modified Gorham process (such asatmospheric pressure chemical vapour deposition) is used for thedeposition of parylene on a liquid layer with a liquid vapour pressuregreater than 7 Pa. In that situation, an inert carrier gas from gassource 101 is utilized to transport the polymeric dimer and monomerthrough vaporization chamber 102 and pyrolysis chamber 103 to thereactor chamber 105. The injection of an inert gas increases thepressure in the reactor chamber. This protects the liquid layer againstvaporization. Suitable inert gases are argon, helium, and nitrogen, forexample.

For the conventional thermal deposition process, such as for parylenedeposition, the vaporization chamber 101 vaporizes a solid paryleneprecursor, for example a stable di-cyclic dimer, di-p-xylylene, orhalogenated derivatives at temperatures between 110° and 200° C. Thevaporized precursor then passes to the pyrolysis chamber 102 todecompose the dimer in reactive species, such as monomers, attemperatures between 400° C. and 700° C. For dichloro-p-xylylene,typical parameters are 150° C. for the vaporization and 650° C. for thepyrolysis. The pyrolized precursor then passes from the pyrolysischamber 103 to the medical devices to be treated on a sample holder 110in the deposition chamber 105. Typical parylene layer thickness isbetween 10 nm-100 microns. The precursor vapour pressure in thedeposition chamber 105 is approximately between 1 and 10 Pa, typically 7Pa, and the substrate temperature is substantially at room temperature.The remaining vapour mixture then passes from deposition chamber 105through valve 106 to a cold trap 107 connected to a vacuum pump 108. Forpolymer deposition the valves 116 and 106 are open.

For liquid layer deposition, valves 116 and 106 are closed. In a numberof constructions, the liquid to be deposited on the medical devices isplaced in liquid chamber 114. Evaporation of the liquid is controlledthrough energy source 113 such as a thermal system or an ultravioletlight source system. The evaporation rate can be controlled through theamount of energy introduced from energy source 113 to the liquid chamber114. Another factor for the quantity of the vaporized liquid to beintroduced depends on the size of the liquid chamber 114. Typically, athin homogeneous pinhole-free liquid layer of 10 nm to 500 microns isdesirable. During liquid layer deposition, valve 112 is open. The energysource 113 evaporates the liquid, which then condenses on the medicaldevices placed on sample holder 110. The valve 115 allows pumping theliquid chamber 114 regardless of the deposition chamber 105. To protectthe vacuum pump 108, fluid exiting through valve 115 passes through coldtrap 107.

In some constructions, co-evaporation of specific species is obtained,such as by combining elements chemically or physically with a type ofparylene or other polymer simultaneously. In that situation, valves 116and 106 remain open while valve 112 is open.

In other constructions, the liquid is applied as a fog or a mist. Instill further constructions, the liquid is applied by dipping, castingor dispensing. In this situation, the medical devices having a least oneprotective layer already deposited on them are taken out of reactor 105and dipped or otherwise treated with liquid. The medical devices arethen raised above or away from the liquid to drain excrescent liquid,for an amount of time that depends on the desired thickness of theliquid layer. When additional protective layers are to be deposited,then the medical devices are returned to the reactor 105. The processcan be reiterated until the desired behavior and thickness of hermeticbarrier is achieved.

The liquid or liquids selected for use according to the presentinvention should be biocompatible to protect patients from inflammationor other hazardous tissue reaction in the event of defects arising inone or more layers. The liquid, such as a biocompatible oil, should havegood wetability properties to create a thin, conformal homogeneouspinhole-free liquid layer of typically 10 nm to 500 microns on anunderlying polymeric or inorganic layer. Depending on thehydrophobic-hydrophilic, lipophobic-lipophilic and/or other propertiesof the liquid, the medical device coated according to the presentinvention is more readily protected against corrosion and/ordegradation, etc. The liquid or liquids can also provide a storagefunction, such as by absorbing specific atoms, ions or molecules likeoxygen, water and/or types of molecules. Such properties arebi-directional, thereby protecting the patient as well as whatevercomponents and substrate of the medical device are coated according tothe present invention. For certain medical applications, at least oneliquid layer contains at least one pharmaceutical or other active agentto protect against infection and/or inflammation, or to improveimplant-tissue adhesion or acceptance. An outer layer such as anamorphous structure, such as an amorphous parylene layer, can serve as adrug releasing membrane to provide controlled release of an active agentthrough the amorphous layer. The amorphous layer can by created forexample by a plasma enhanced chemical vapour deposition.

An in-situ plasma enhanced chemical vapour deposition process can alsobe utilized. Controlled plasma is formed adjacent to the medical devicewafers by RF energy applied to sample holder 110 from RF generator 109,with the deposition chamber 105 grounded, via a high frequency sealed bya pass-through connector 111. RF generator 109 can supply at a high RFfrequency of typically 13.56 MHz or 2.45 GHz to the sample holder 110 toenhance the decomposition and/or excitation of reactive speciesintroduced into chamber. A gas source 104 is connected to depositionchamber 105 to introduce one or more gases in the plasma process, forsurface treatment or precursor interaction, such as recombination,excitation or dissociation.

Layer on substrate adhesion or layer on layer adhesion could be improvedby different processes. Typically for parylene adhesion, either onsubstrate or on layer, but not limited to, silanization or gas plasmatreatment are used. For example oxygen, nitrogen or air plasma isapplied directly in the deposition chamber 103 before coating. Further,other adhesion layer or plasma enhanced deposition layer can be used.Preferably, a well known adhesion layer based on silanes are composed ofvinyl trichlorosilane in either xylene, isopropyl alcohol or achlorofluorocarbon gas. Alternatively,gammamethacryloxypropyltrimethoxysilane in a methanol-water solvent havebeen successfully used. Silanes can also be vapour phase applied ifnon-liquid application is preferred.

Thus, while there have been shown, described, and pointed outfundamental novel features of the invention as applied to a preferredembodiment thereof, it will be understood that various omissions,substitutions, and changes in the form and details of the devicesillustrated, and in their operation, may be made by those skilled in theart without departing from the spirit and scope of the invention. Forexample, it is expressly intended that all combinations of thoseelements and/or steps that perform substantially the same function, insubstantially the same way, to achieve the same results be within thescope of the invention. Substitutions of elements from one describedembodiment to another are also fully intended and contemplated. It isalso to be understood that the drawings are not necessarily drawn toscale, but that they are merely conceptual in nature. It is theintention, therefore, to be limited only as indicated by the scope ofthe claims appended hereto.

Every issued patent, pending patent application, publication, journalarticle, book or any other reference cited herein is each incorporatedby reference in their entirety.

1. An implantable medical device comprising: a plurality of componentson a substrate; and a biocompatible multi-layer coating applied at leastin part by vapour deposition to conform to and sealingly cover at leasta portion of the components and the substrate, the coating being appliedin at least two sets of layers, wherein each set has at least one layerformed by dissociation of a polymeric precursor and then deposition ofthat dissociated precursor, and another layer is a biocompatible liquid,and further wherein each of the sets has at least three layers, anddiffusion through each layer differs from that of the other layers inthe set.
 2. The implantable medical device of claim 1 wherein each layerdiffers in at least one diffusion barrier property from the other layerin the set.
 3. The implantable medical device of claim 1 whereindiffusion through each layer differs from that of the other layer in theset and adds to the overall barrier effect of the coating.
 4. Theimplantable medical device of claim 1 wherein the precursor for at leastone set is selected from di-p-xylylene and halogenated derivativesthereof.
 5. The implantable medical device of claim 4 wherein theprecursor is dichloro-p-xylylene.
 6. The implantable medical device ofclaim 1 wherein at least one of the layers enhances wetability of thelayer beneath it.
 7. The implantable medical device of claim 6 whereinthe wetability-enhancing layer includes at least one of chemical andplasma activation of the layer beneath it.
 8. The implantable medicaldevice of claim 1 wherein the liquid is applied by condensation.
 9. Theimplantable medical device of claim 1 wherein the liquid is applied as afog or a mist.
 10. The implantable medical device of claim 1 wherein theliquid is applied by dipping or casting.
 11. The implantable medicaldevice of claim 1 wherein at least one of the layers in each set is aplasma-enhanced parylene polymer.
 12. The implantable medical device ofclaim 1 wherein at least one liquid layer includes an active agent. 13.The implantable medical device of claim 1 wherein the plurality ofcomponents have at least a first three-dimensional portion, and thecoating conforms to and sealingly covers at least the first portion ofthe components.
 14. The implantable medical device of claim 13 whereinthe multi-layer coating conforms to and sealingly covers at leastsubstantially all of the components.
 15. The implantable medical deviceof claim 1 wherein a barrier property for the transport of impurities isdominated more by the interface between adjacent layers than by thethickness of each individual layer.
 16. An implantable medical devicecomprising: a plurality of components on a substrate having at least afirst three-dimensional portion; and a biocompatible multi-layer coatingapplied at least in part by vapour deposition to conform to andsealingly cover at least the first portion of the components and thesubstrate, the coating being applied in at least two sets of layers,wherein each set has at least one layer formed by dissociation of apolymeric precursor and then deposition of that dissociated precursor,and another layer is a biocompatible liquid, and wherein a barrierproperty for the transport of impurities is dominated more by theinterface between adjacent layers than by the thickness of eachindividual layer, and further wherein each of the sets has at leastthree layers, and diffusion through each layer differs from that of theother layers in the set.
 17. The implantable medical device of claim 16wherein the multi-layer coating conforms to and sealingly covers atleast substantially all of the components and the substrate.